CENPF调控PI3K/AKT信号通路影响唾液腺腺样囊性癌进展  

Impact of CENPF on Progression of Adenoid Cystic Carcinoma through Regulation of PI3K/AKT Signaling Pathway

作　　者：杨心怡 黄薇薇 黄丽 胡赟 YANG Xinyi;HUANG Weiwei;HUANG Li;HU Yun(School of Stomatology,Guizhou Medical University,Guiyang 550004,China;Department of Pathology,Stomatological Hospital of Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学口腔医学院,贵州贵阳550004 [2]贵州医科大学附属口腔医院病理科,贵州贵阳550004

出　　处：《口腔医学研究》2024年第9期803-809,共7页Journal of Oral Science Research

基　　金：贵州省卫健委科学技术基金项目(编号:gzwjwkj2020-1-174)。

摘　　要：目的:探讨着丝粒蛋白F(centromere protein F,CENPF)在腺样囊性癌(adenoid cystic carcinoma,ACC)发生发展中的作用和分子机制。方法:通过小干扰RNA转染敲低ACC细胞中的CENPF。通过细胞计数试剂盒(cell counting kit-8,CCK-8)、划痕实验和Transwell测定评估敲低CENPF对ACC细胞增殖、迁移、侵袭的影响;通过蛋白免疫印迹实验分析改变CENPF表达后ACC细胞中磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase,PI3K)/丝氨酸/苏氨酸蛋白激酶(serine/threonine protein kinase,AKT)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路相关蛋白表达变化,通过CCK-8、划痕实验和Transwell测定评估敲低CENPF联合PI3K抑制剂BKM-120对ACC细胞增殖、迁移、侵袭的影响。结果:敲低ACC-M中CENPF表达后,CCK-8实验证明其增殖能力减弱;划痕实验表明其迁移能力减弱,Transwell实验表明其侵袭能力减弱,PI3K/AKT通路关键蛋白p-PI3K、p-AKT和p-mTOR蛋白表达水平下降。在下调CENPF的ACC-M中加入PI3K抑制剂,PI3K/AKT通路关键蛋白表达水平进一步下降。此外,加入PI3K抑制剂后,CENPF下调的ACC-M增殖、迁移、侵袭能力较单纯下调CENPF的ACC-M进一步减弱。结论:CENPF通过调控PI3K/AKT信号通路参与ACC进展。Objective:To investigate the role and molecular mechanisms of CENPF in the pathogenesis and development of adenoid cystic carcinoma(ACC).Methods:CENPF in ACC cells was knocked down by transfection with small interfering RNA(siRNA).The effects of CENPF knockdown on the proliferation,migration,and invasion of ACC cells were evaluated using CCK-8,scratch assay,and transwell assay,respectively.Changes in the activity of phosphatidylinositol-3-kinase/serine/threonine protein kinase/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway-related proteins in ACC cells after altering CENPF expression were analyzed by Western blot.Finally,the combined effect of CENPF knockdown and PI3K inhibitor BKM-120 on the proliferation,migration,and invasion of ACC cells was assessed using CCK-8,scratch assay,and transwell assay.Results:Knockdown of CENPF expression in ACC-M cells resulted in decreased proliferation,migration,and invasion abilities as demonstrated by CCK-8,scratch assay,and transwell assay,respectively.The expression levels of key proteins in the PI3K/AKT pathway,including p-PI3K,p-AKT,and p-mTOR,were reduced.Furthermore,the expression levels of these proteins further decreased when PI3K inhibitor was added to CENPF-knockdown ACC-M cells.Additionally,the proliferation,migration,and invasion abilities of ACC-M cells with CENPF knockdown were further weakened when PI3K inhibitor was added compared to CENPF knockdown alone.Conclusion:CENPF regulates the progression of ACC by modulating the PI3K/AKT signaling pathway.

关 键 词：着丝粒蛋白F 腺样囊性癌 PI3K/AKT信号通路 机制研究 

分 类 号：R739.8[医药卫生—肿瘤]